A three-lncRNA signature of pretreatment biopsies predicts pathological response and outcome in esophageal squamous cell carcinoma with neoadjuvant chemoradiotherapy.

Background: Current strategies are insufficient to predict pathologically complete response (pCR) for esophageal squamous cell carcinomas (ESCCs) before treatment. Here, we aim to develop a novel long noncoding RNA (lncRNA) signature for pCR and outcome prediction of ESCCs through a multicenter analysis for a Chinese population.

Methods: Differentially expressed lncRNAs (DELs) between pCRs and less than pCR (
Results: Twelve DELs were identified from Guangzhou cohort and six lncRNAs were verified. Then, a classifier of three lncRNAs (SCAT1, PRKAG2-AS1, and FLG-AS1) was established and achieved a high accuracy with an area under the receiver operating characteristic curve (AUC) of 0.952 in the training cohort, which was well validated in the internal validation cohort and external cohort with the AUCs of 0.856 and 0.817, respectively. Furthermore, the predictive score was identified as the only independent predictor for pCR. Patients with high discriminant score showed a significantly longer overall and relapse-free survival (P < .05).

Conclusions: We developed the first and applicable three-lncRNA signature of pCR and outcome prediction, which is robust and reproducible in multicenter cohorts for ESCCs with nCRT.